{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T18:05:34Z","timestamp":1775844334230,"version":"3.50.1"},"reference-count":36,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Amodiaquine-artesunate is one of the recommended options by the Angolan National Malaria Control Program for the treatment of uncomplicated malaria and for malaria seasonal chemoprevention. CYP2C8 is a critical enzyme in the metabolism of amodiaquine. The\n                    <jats:italic>CYP2C8<\/jats:italic>\n                    gene harbors alleles coding for less active enzymes that have been linked to amodiaquine-associated adverse events. In this work, we analyzed the prevalences of the\n                    <jats:italic>CYP2C8<\/jats:italic>\n                    main alleles in a sample of the Angolan population. We found an expected robust frequency of a very-low-activity allele,\n                    <jats:italic>CYP2C8*2<\/jats:italic>\n                    (18.2%) but also the unusual presence of alleles\n                    <jats:italic>CYP2C8*3<\/jats:italic>\n                    (1%) and\n                    <jats:italic>CYP2C8*4<\/jats:italic>\n                    (0.5%). Together, these alleles were seen in a non-negligible group of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    malaria patients and children under amodiaquine-based therapies and prophylactic strategies.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.24-0710","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:57:22Z","timestamp":1764874642000},"page":"302-304","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence in Northern Angola of Cytochrome P450 (CYP) 2C8 Alleles Associated with Amodiaquine Decreased Metabolism"],"prefix":"10.4269","volume":"114","author":[{"given":"Kinanga","family":"Kiaco","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, UNL, Lisboa, Portugal;"},{"name":"Servi\u00e7os de Sa\u00fade das For\u00e7as Armadas Angolanas, Estado Maior General das For\u00e7as Armadas, Luanda, Angola;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tais","family":"N\u00f3brega de Sousa","sequence":"additional","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Brazil;"},{"name":"Host-Microbe Section, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virg\u00edlio do","family":"Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, UNL, Lisboa, Portugal;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, UNL, Lisboa, Portugal;"},{"name":"Host-Microbe Section, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden;"},{"name":"Tropical Medicine Unit, Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Nova University of Lisbon, Lisbon, Portugal;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinora","family":"Lopes","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa, UNL, Lisboa, Portugal;"},{"name":"Tropical Medicine Unit, Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Nova University of Lisbon, Lisbon, Portugal;"},{"name":"Science and Community Support Service (SACC), Institute of Hygiene and Tropical Medicine, Nova University of Lisbon, Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","article-title":"World Malaria Report 2019.","year":"2019"},{"key":"b2","series-title":"J Pharmacol Exp Ther","first-page":"399","article-title":"Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: A new high affinity and turnover enzyme-specific probe substrate","volume":"300","author":"Li","year":"2002"},{"key":"b3","series-title":"BMC Med","first-page":"47","article-title":"The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: A meta-analysis of individual patient data","volume":"18","author":"Bretscher","year":"2020"},{"key":"b4","series-title":"Expert Opin Drug Metab Toxicol","first-page":"39","article-title":"An update on pharmacogenetic factors influencing the metabolism and toxicity of artemisinin-based combination therapy in the treatment of malaria","volume":"18","author":"Pernaute-Lau","year":"2022"},{"key":"b5","series-title":"Pharmacogenomics J","first-page":"247","article-title":"The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals","volume":"22","author":"Haeggstr\u00f6m","year":"2022"},{"key":"b6","series-title":"Hum Genomics","first-page":"40","article-title":"Meta-analysis of the global distribution of clinically relevant CYP2C8 alleles and their inferred functional consequences","volume":"18","author":"Camara","year":"2024"},{"key":"b7","series-title":"Biochem Pharmacol","first-page":"1113","article-title":"The bioactivation of amodiaquine by human polymorphonuclear leucocytes in\u00a0vitro: Chemical mechanisms and the effects of fluorine substitution","volume":"50","author":"Tingle","year":"1995"},{"key":"b8","series-title":"Clin Pharmacol Ther","first-page":"197","article-title":"Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: Implications for malaria treatment in Africa","volume":"82","author":"Parikh","year":"2007"},{"key":"b9","series-title":"Malar J","first-page":"90","article-title":"Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar","volume":"20","author":"Pernaute-Lau","year":"2021"},{"key":"b10","series-title":"Eur J Clin Pharmacol","first-page":"15","article-title":"CYP2C8 polymorphism frequencies among malaria patients in Zanzibar","volume":"61","author":"Cavaco","year":"2005"},{"key":"b11","series-title":"Drug Metab Pharmacokinet","first-page":"165","article-title":"Functional role of Ile264 in CYP2C8: Mutations affect haem incorporation and catalytic activity","volume":"23","author":"Singh","year":"2008"},{"key":"b12","series-title":"Malar J","first-page":"396","article-title":"Malaria in Angola: Recent progress, challenges and future opportunities using parasite demography studies","volume":"21","author":"Tavares","year":"2022"},{"key":"b13","series-title":"Antimicrob Agents Chemother","first-page":"e0152523","article-title":"Therapeutic response to four artemisinin-based combination therapies in Angola, 2021","volume":"68","author":"Dimbu","year":"2024"},{"key":"b14","series-title":"J Infect Dis","first-page":"e1119","article-title":"Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections","volume":"231","author":"Fan\u00e7ony","year":"2025"},{"key":"b15","series-title":"Malar J","first-page":"504","article-title":"Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola","volume":"14","author":"Kiaco","year":"2015"},{"key":"b16","series-title":"Malar J","first-page":"383","article-title":"The drug transporter ABCB1 c.3435C>T SNP influences artemether-lumefantrine treatment outcome","volume":"16","author":"Kiaco","year":"2017"},{"key":"b17","series-title":"Clin Chem Lab Med","first-page":"168","article-title":"CYP2C8 polymorphism among the Portuguese","volume":"44","author":"Cavaco","year":"2006"},{"key":"b18","series-title":"History of East Africa","first-page":"576","author":"Low","year":"1976"},{"key":"b1","article-title":"World Malaria Report 2019.","year":"2019"},{"key":"b2","series-title":"J Pharmacol Exp Ther","first-page":"399","article-title":"Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: A new high affinity and turnover enzyme-specific probe substrate","volume":"300","author":"Li","year":"2002"},{"key":"b3","series-title":"BMC Med","first-page":"47","article-title":"The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: A meta-analysis of individual patient data","volume":"18","author":"Bretscher","year":"2020"},{"key":"b4","series-title":"Expert Opin Drug Metab Toxicol","first-page":"39","article-title":"An update on pharmacogenetic factors influencing the metabolism and toxicity of artemisinin-based combination therapy in the treatment of malaria","volume":"18","author":"Pernaute-Lau","year":"2022"},{"key":"b5","series-title":"Pharmacogenomics J","first-page":"247","article-title":"The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals","volume":"22","author":"Haeggstr\u00f6m","year":"2022"},{"key":"b6","series-title":"Hum Genomics","first-page":"40","article-title":"Meta-analysis of the global distribution of clinically relevant CYP2C8 alleles and their inferred functional consequences","volume":"18","author":"Camara","year":"2024"},{"key":"b7","series-title":"Biochem Pharmacol","first-page":"1113","article-title":"The bioactivation of amodiaquine by human polymorphonuclear leucocytes in\u00a0vitro: Chemical mechanisms and the effects of fluorine substitution","volume":"50","author":"Tingle","year":"1995"},{"key":"b8","series-title":"Clin Pharmacol Ther","first-page":"197","article-title":"Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: Implications for malaria treatment in Africa","volume":"82","author":"Parikh","year":"2007"},{"key":"b9","series-title":"Malar J","first-page":"90","article-title":"Influence of cytochrome P450 (CYP) 2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment of uncomplicated Plasmodium falciparum malaria in Zanzibar","volume":"20","author":"Pernaute-Lau","year":"2021"},{"key":"b10","series-title":"Eur J Clin Pharmacol","first-page":"15","article-title":"CYP2C8 polymorphism frequencies among malaria patients in Zanzibar","volume":"61","author":"Cavaco","year":"2005"},{"key":"b11","series-title":"Drug Metab Pharmacokinet","first-page":"165","article-title":"Functional role of Ile264 in CYP2C8: Mutations affect haem incorporation and catalytic activity","volume":"23","author":"Singh","year":"2008"},{"key":"b12","series-title":"Malar J","first-page":"396","article-title":"Malaria in Angola: Recent progress, challenges and future opportunities using parasite demography studies","volume":"21","author":"Tavares","year":"2022"},{"key":"b13","series-title":"Antimicrob Agents Chemother","first-page":"e0152523","article-title":"Therapeutic response to four artemisinin-based combination therapies in Angola, 2021","volume":"68","author":"Dimbu","year":"2024"},{"key":"b14","series-title":"J Infect Dis","first-page":"e1119","article-title":"Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections","volume":"231","author":"Fan\u00e7ony","year":"2025"},{"key":"b15","series-title":"Malar J","first-page":"504","article-title":"Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola","volume":"14","author":"Kiaco","year":"2015"},{"key":"b16","series-title":"Malar J","first-page":"383","article-title":"The drug transporter ABCB1 c.3435C>T SNP influences artemether-lumefantrine treatment outcome","volume":"16","author":"Kiaco","year":"2017"},{"key":"b17","series-title":"Clin Chem Lab Med","first-page":"168","article-title":"CYP2C8 polymorphism among the Portuguese","volume":"44","author":"Cavaco","year":"2006"},{"key":"b18","series-title":"History of East Africa","first-page":"576","author":"Low","year":"1976"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/114\/2\/article-p302.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/114\/2\/article-p302.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/114\/2\/article-p302.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:19:35Z","timestamp":1775841575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/114\/2\/article-p302.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":36,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.24-0710","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}